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October 24, 2025Biomarker ResearchOpen Access

Lactate and lactylation: molecular insights into histone and non-histone lactylation in tumor progression, tumor immune microenvironment, and therapeutic strategies

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Authors

KSKai SunGeneral CardiologyQHQibo HuangTongji HospitalQLQilin LiCentral South University

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Implication

Narrative review uncovers the molecular mechanisms of histone and nonhistone lactylation in cancer, highlighting novel therapeutic targets in the tumor immune microenvironment.

Key Points

  • To comprehensively review lactate metabolism, transport, and protein lactylation mechanisms, assessing their roles in tumor progression, immune modulation, and therapeutic potential.
  • Reviewed literature on lactate biosynthesis, compartmentalized transport, and the structural networks of lactate dehydrogenases, transporters, lactyltransferases, and deacetylases.
  • Evaluated oncogenic signaling pathways, transcriptional networks, and immune microenvironment alterations regulated by histone and non-histone lactylation across cancer subtypes.
  • Lactate functions beyond a glycolytic byproduct by mediating histone and non-histone lactylation, driving oncogenic signaling and metabolic reprogramming.
  • Enzymatic networks regulating lactylation remodel the tumor immune microenvironment to promote immunosuppression and malignant progression.
  • Targeting lactate shuttles, lactylation-modifying enzymes, and downstream transcriptional signatures presents viable avenues to enhance cancer therapeutic efficacy.

Cite This Study

Sun et al. (2025) studied this question.

synapsesocial.com/papers/6a7df81733dcb27c99cb6422https://doi.org/10.1186/s40364-025-00849-0
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Also Consider

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  1. 1Lactate activates CCL18 expression via H3K18 lactylation in macrophages to promote tumorigenesis of ovarian cancer2024 · 50 citations
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  4. 4Histone Lactylation-Driven GPD2 Mediates M2 Macrophage Polarization to Promote Malignant Transformation of Cervical Cancer Progression2024 · 41 citations
  5. 5Effects of the Acetyltransferase p300 on Tumour Regulation from the Novel Perspective of Posttranslational Protein Modification2023 · 75 citations